This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The interactions between membrane proteins and the phospholipids that constitute the majority of cell membranes will be examined, paying particular attention to the roles of polyunsaturated fatty acids (PUFAs) that are known to have wide-ranging impacts on human health. We will reveal the mechanisms by which PUFAs modulate protein structure and function. We employ three important, yet markedly different prototypical systems to understand these effects: rhodopsin, the KcsA potassium channel, and a pentameric ligand-gated ion channel receptor. Using Anton, we will perform systematic multi-microsecond studies of different lipid compositions to understand PUFA effects on protein structure and fluctuations.